DNA glycosylase activity and cell proliferation are key factors in modulating homologous recombination in vivo.

ABSTRACT: Cancer susceptibility varies between people, affected by genotoxic exposures, genetic makeup and physiological state. Yet, how these factors interact among each other to define cancer risk is largely unknown. Here, we uncover the interactive effects of genetical, environmental and physiological factors on genome rearrangements driven by homologous recombination (HR). Using FYDR mice to quantify HR-driven rearrangements in pancreas tissue, we show that DNA methylation damage (induced by methylnitrosourea) and cell proliferation (induced by thyroid hormone) each induce HR and together act synergistically to induce HR-driven rearrangements in vivo. These results imply that developmental or regenerative proliferation as well as mitogenic exposures may sensitize tissues to DNA damaging exposure

SUBMITTER: Kiraly O 

PROVIDER: S-EPMC4216056 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature